Virtual Library
Start Your Search
Jong-Seok Lee
Author of
-
+
MA08 - Clinical Trials in Brain Metastases (ID 906)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
-
+
MA08.07 - Real World Data of Osimertinib in Patients with Central Nervous System (CNS) Metastasis in ASTRIS Korean Subset. (ID 13581)
15:50 - 15:55 | Author(s): Jong-Seok Lee
- Abstract
- Presentation
Background
More than 40% of non-small cell lung cancer (NSCLC) patients develop CNS metastasis in their lifetime. Osimertinib is a third-generation EGFR-TKI which selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations. Clinical studies have shown superior efficacy of osimertinib in CNS compared to platinum chemotherapy. Treatment efficacy in patients with or without CNS metastasis were observed within the second interim analysis of ASTRIS (NCT02474355). Data cut-off (DCO) was 20 October 2017.
a9ded1e5ce5d75814730bb4caaf49419 Method
In ASTRIS, advanced NSCLC patients with a locally confirmed T790M mutation, WHO performance status 0-2, prior EGFR-TKI therapy were enrolled. Patients with stable CNS metastases were allowed. The primary endpoint was overall survival (OS); other endpoints included investigator-assessed response rate (RR), progression-free survival (PFS), time to treatment discontinuation (TTD) and safety. These endpoints were also analyzed according to presence of CNS metastasis.
4c3880bb027f159e801041b1021e88e8 Result
A total of 466 patients received at least one dose of osimertinib 80mg from 31 Korean sites. CNS metastasis was evaluated in 310 patients and was present in 211 (68.1%) patients (CNS-met); 181 brain only, 1 leptomeningeal only, 29 both. 99 (31.9%) patients did not have CNS metastasis (CNS-no), and 155 patients were not evaluated (CNS-ne). At DCO, 236 patients (50.6%) were ongoing and median duration of exposure was 11.2 (0–19) months. In patients evaluable for response, defined as at least one dose of osimertinib and one response assessment, RR was 71.0% (320/451; 95% CI, 66.5–75.1): Patients with (N=211), without (N=99), and not-evaluated CNS metastasis (N=155) had RR of 68% (134/197; 95% CI, 61.0-74.5), 79.6% (78/98; 95% CI, 70.3-87.1), and 69.7% (108/155; 95% CI, 61.8-76.8), respectively. Median PFS was 12.4 months (95% CI, 11.1-13.6 months); 10.8 months (95% CI, 9.5-11.5) in CNS-met,11.0 months (95% CI, 9.2-14.5) in CNS-no, and 15.1 months (95% CI, 13.6-18.2) in CNS-ne. Median TTD was 16.5 months (95% CI, 14.1-NC); 11.2 months (95% CI, 9.4-14.8) in CNS-met, 14.7 months (95% CI, 12.2-NC) in CNS-no, and NC (95% CI, 15.5-NC) in CNS-ne. OS was not reached (data maturity: 19.7%). Serious adverse event (AE) regardless of causality were reported in 116 patients (24.9%) and AEs leading to death in 13 patients (2.8%). ILD/pneumonitis-like events were reported in 8 patients (1.7%), and QTc prolongation in 7 patients (1.5%).
8eea62084ca7e541d918e823422bd82e Conclusion
In ASTRIS Korean subset, patients with or without CNS metastasis had comparable efficacy outcome. This data continues to support osimertinib’s clinical benefit on EGFRm T790M NSCLC patients with CNS metastasis.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MA11 - Biomarkers of IO Response (ID 912)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
-
+
MA11.07 - Expression of LAG-3 and NY-ESO-1 In Tumor Cells is Promising Biomarker Predicting Durable Clinical Benefit of PD-1 Blockade in Advanced NSCLC (ID 12403)
11:10 - 11:15 | Author(s): Jong-Seok Lee
- Abstract
- Presentation
Background
Anti-PD-1 antibodies are currently used in treating advanced non-small cell lung cancer (NSCLC). PD-L1 expression in tumor cell or immune cell is the only available predictive biomarker in the clinic. Lymphocyte activation gene-3 (LAG-3) is an inhibitory checkpoint in immune cells and NY-ESO-1 is an antigen expressed in tumor cells. We investigated LAG-3 and NY-ESO-1 protein expression and its relationship to response to anti-PD-1 therapy in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed the medical records of 38 patients with advanced NSCLC who were enrolled in prospective clinical trials of nivolumab or pembrolizumab monotherapy (NCT01295827, NCT01905657, and NCT02175017) between October 2013 and April 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital. Immunohistochemial staining (IHC) of NY-ESO-1(E978, Invitrogen), and PD-L1 (22C3, Dako) in tumor cell and LAG-3(EPR4392, Abcam) in immune cell was performed to determine protein expression.
4c3880bb027f159e801041b1021e88e8 Result
LAG-3 and NY-ESO-1 protein expression were assessed in 38 patients. LAG-3, NY-ESO-1 and PD-L1 were expressed in 76.3% (29/38), 50% (19/38) and 18.5% (7/36, 50% cut-off value), respectively. Sixteen patients with durable clinical benefit (DCB, anti-PD-1 therapy more than 6-month) were grouped as responder. NY-ESO-1 expression (DCB 11/19 vs 5/19, p= .05) and LAG-3 expression (DCB 16/29 vs 0/9, p= .003) were significantly correlated with the DCB to Anti-PD-1 therapy, while PD-L1 expression was identified in 5 patients with DCB (5/7 vs 11/29, p= .12). Patients with both NY-ESO-1 and LAG-3 expression had high rate of DCB (73.3%, 11/15 pts). With the results of the interaction with DCB, the calculation of positive predictive value and negative predictive value about durable clinical benefit is assessed and the significance of each measurement was proven by Fisher’s exact test. As a result, NPV of LAG-3 expression in tumor cell was 100% and PPV of each protein expression was LAG-3 (55.17%), NY-ESO-1(57.89%) and PD-L1 (71.43%) respectively. In survival analysis, LAG-3 expression was a significant predictor for PFS (HR 0.170; CI 0.066-0.437; p< .0001) and OS (HR 0.250; CI 0.140-0.599; p= .002).
8eea62084ca7e541d918e823422bd82e Conclusion
NY-ESO-1 expression on tumor tissue and LAG-3 expression on tumor microenvironment may be useful for identifying advanced NSCLC patients for the treatment of anti-PD-1 therapy. These protein markers seem quite promising and warrant further investigation in large sample size.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MA26 - New Therapies and Emerging Data in ALK, EGFR and ROS1 (ID 930)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 201 BD
-
+
MA26.09 - Lazertinib, a Third Generation EGFR-TKI, in Patients with EGFR-TKI-Resistant NSCLC: Updated Results of a Phase I/II Study (ID 12817)
14:30 - 14:35 | Author(s): Jong-Seok Lee
- Abstract
- Presentation
Background
Lazertinib (YH25448) is a highly mutant-selective, irreversible 3rd-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that can penetrate the blood-brain barrier, and targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type. We report the updated results from a Phase I/II study of lazertinib (NCT03046992)
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with advanced and metastatic NSCLC who had progressed after treatment with EGFR-TKIs with/without asymptomatic brain metastases (BM) were enrolled in an open-label, multicenter, phase I/II study with dose-escalation and expansion cohorts. Lazertinib was administered once daily at doses between 20 to 320 mg in a 21-day cycle. Patients were assessed for safety, tolerability, pharmacokinetics and efficacy. T790M status was confirmed in the dose-expansion cohorts.
4c3880bb027f159e801041b1021e88e8 Result
A total of 115 patients (median age 62 years, female 62%) were enrolled. The dose-escalation cohort included 38 patients administered with 20 to 320 mg across 7 dose levels, and 77 patients in the dose-expansion cohort were administered with 40 to 240 mg across 5 dose levels. No dose-limiting toxicities were observed in the dose-escalation cohort. Systemic exposure increased dose-dependently. Of the evaluable patients (n=110) at data cut-off, the objective response rate (ORR) was 65% (95% confidence interval [CI], 54.9 to 73.4). The ORR for 93 of the T790M+ patients was 69% (95% CI, 58.4 to 78.0). In patients with BM (n=12), the intracranial ORR was 50% (95% CI, 21.1 to 78.9). The most common treatment-emergent adverse events (TEAEs) were pruritus (19%), decreased appetite (17%), rash (14%), and constipation (12%). The most frequently reported TEAEs of grade ≥ 3 were hyponatraemia (2%), nausea (2%) and pneumonia (2%).
ORR in T790M+ patients Dose QD 20 mg 40 mg 80 mg 120 mg 160 mg 240 mg Evaluable patients*, n 2 25 18 22 18 8 ORR, n (%) 2 (100) 17 (68) 11 (61) 17 (77) 11 (61) 6 (75) * Patients were deemed evaluable for response if they underwent a post-baseline radiological assessment (RECIST 1.1) or were discontinued prior to the post-baseline assessment.
8eea62084ca7e541d918e823422bd82e Conclusion
Lazertinib was safe, well-tolerated and exhibited promising systemic and intracranial antitumor activity in EGFR T790M+ NSCLC patients. The dose-expansion cohort as the first and second-line setting has been initiated from April 2018.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)
- Event: WCLC 2018
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
-
+
PL02.03 - Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) (ID 11155)
08:30 - 08:40 | Author(s): Jong-Seok Lee
- Abstract
- Presentation
Background
Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).
This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).
275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.
Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.
BIRC-Assessed Endpoint, % Brigatinib
(n=137)
Crizotinib
(n=138)
P-Value All patients ORRa 76 (68–83b) 73 (65–80b) Confirmed ORR 71 (62–78b) 60 (51–68b) 0.0678 With any intracranial CNS metastases (n=43) (n=47) iORRa 79 (64–90b) 23 (12–38b) Confirmed iORR 67 (51–81b) 17 (8–31b) <0.0001 Median iPFS, months NR (11–NRb) 6 (4–9b) 1-year iPFS 67 (47–80b) 21 (6–42b) HR 0.27 (0.13–0.54) <0.0001c With measurable intracranial CNS metastases (n=18) (n=21) iORRa 83 (59–96b) 33 (15–57b) Confirmed iORR 78 (52–94b) 29 (11–52b) 0.0028 aResponse, ≥1 assessment; b95% CI; cLog-rank.
a9ded1e5ce5d75814730bb4caaf49419Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
